Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections

Versteeg, Leroy; Almutairi, Mashal M.; Hotez, Peter J.; Pollet, Jeroen

doi:10.3390/vaccines7040122

Cited by 69 publications

(53 citation statements)

References 88 publications

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“…Over the last decade, messenger RNA (mRNA) has emerged as a new platform technology for the development of vaccines not just for anti-cancer therapeutics but also against infectious diseases. As reviewed in the accompanying manuscript by Versteeg et al, there is now even progress in the challenging development of mRNA vaccines against parasitic infections where a low-cost and high-throughput vaccine development platform is urgently needed [1].…”

Section: Introductionmentioning

confidence: 99%

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Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

et al. 2019

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The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to traditional vaccine development platforms, and thus there is less clarity regarding the criteria needed to ensure regulatory compliance and acceptance. Generally, to identify the ideal product characteristics, a series of assays needs to be developed, qualified and ultimately validated to determine the integrity, purity, stability, and reproducibility of a vaccine target. Here, using the available literature, we provide a summary of the array of biophysical and biochemical assays currently used in the field to characterize mRNA vaccine antigen candidates. Moreover, we review various in vitro functional cell-based assays that have been employed to facilitate the early assessment of the biological activity of these molecules, including the predictive immune response triggered in the host cell. Messenger RNA vaccines can be produced rapidly and at large scale, and thus will particularly benefit from well-defined and well-characterized assays ultimately to be used for in-process, release and stability-indications, which will allow equally rapid screening of immunogenicity, efficacy, and safety without the need to conduct often lengthy and costly in vivo experiments.

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Section: Introductionmentioning

confidence: 99%

“…As reviewed elsewhere [1,6], mRNA turns cells into antigen production factories; as vaccines, these antigens trigger potent cellular and humoral immune responses.…”

Section: Introductionmentioning

confidence: 99%

Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

et al. 2019

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“…Defining clear product development plans that reflect a vaccine strategy that complements existing control programs will be important in the path to developing effective fluke vaccines. In this respect, researchers working in the fluke vaccine space could consider using similar approaches to the burgeoning efforts currently underway with the COVID-19 vaccine pipeline [ 87 ], such as in vitro transcribed mRNA vaccines, a platform recently advocated for the development of neglected parasitic disease vaccines [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

McManus

2020

Vaccines

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Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause.

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“…Once delivered using an appropriate targeted vaccine delivery system, it can be recognized and internalized by the APCs where the viralderived agents can trigger the innate immune signaling cascades (Fig. 10) 54 .…”

Section: Discussionmentioning

confidence: 99%

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

Pourseif

Parvizpour

Jafari

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 253,381 deaths worldwide since its emergence in late 2019 (updated May 6th, 2020). COVID-19 is caused by a novel emerged coronavirus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. In this study, we have targeted spike (S) glycoprotein, as an important surface antigen of SARS-CoV-2, to identify its immunodominant B- and T-cell epitopes. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in the animal studies.

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Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections

Cited by 69 publications

References 88 publications

Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

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